Viscometer and methods for using the same

ABSTRACT

A viscometer includes a viscosity sensor with a liquid flow channel and at least two pressure sensors positioned along the liquid flow channel and configured to measure a pressure drop of a liquid flowing through the liquid flow channel, and a dispensing mechanism configured to cause dispensing of a liquid from the syringe to the viscosity sensor at a known flow rate. The dispensing mechanism and the viscosity sensor are configured to couple with a syringe configured to contain a liquid. The viscometer further includes an electronic controller configured to control operations of the dispensing mechanism and receive and process data from the viscosity sensor. The viscometer includes a sample loading interface, included in the syringe, through which the viscometer is configured to receive the liquid. The sample loading interface includes a selection valve coupled with, and located between, the viscosity sensor and the syringe.

RELATED APPLICATIONS

This application is a continuation-in-part of International ApplicationNo. PCT/US2015/025417, filed Apr. 10, 2015, which claims priority toU.S. Provisional Patent Application Ser. No. 61/978,735, filed Apr. 11,2014, both of which are incorporated by reference herein in theirentireties.

TECHNICAL FIELD

This application relates generally to viscometers, including but notlimited to viscometers that measure viscosity of liquids utilizing aflow-through type viscosity sensor.

BACKGROUND

Viscosity is a measure of resistance of liquid to flow and its valuedepends on the rate of deformation for Non-Newtonian liquids asdescribed in Dynamics of Polymeric Liquids, Vol. 1, 1987, authored by R.B. Bird, R. C. Armstrong, and O. Hassager. The rate of deformation isgiven by a shear rate in a unit of (time)-1. The viscosity measured at aknown shear rate is “true” viscosity. The dependence of the trueviscosity on shear rate is a viscosity curve which characterizesmaterial and is an important factor to consider for efficientprocessing. However, in many cases, viscosity is measured underill-defined test condition so that shear rate cannot be known orcalculated. Under ill-defined conditions, the measured viscosity valueis only “apparent”. Since the true viscosity is measured at a knownshear rate, the true viscosity is universal whereas the apparentviscosity is not. Instead, the apparent viscosity depends on themeasuring system. For example, as a common practice, a torque of aspindle immersed in a sea of test liquid is measured while the spindleis being rotated at a constant speed. In this case the torque value onlyyields an apparent viscosity since the test condition is ill-defined anda shear rate is not known. At best, the apparent viscosity can bemeasured as a function of the rotational speed of the spindle. Therotational speed of the spindle can be in fact correlated with the shearrate only if a “constitutive equation” for the test liquid is known.However, a “constitutive equation” is not known for almost allNon-Newtonian liquids. Therefore, true viscosity cannot be measured withill-defined test conditions for most non-Newtonian liquids.

Methods of viscosity measurement that give only apparent viscositieshave been developed and used for quality controls in manufacturing andmaterial characterization. Various on-line viscometers are designed forreal time viscosity measurement. U.S. Pat. No. 5,317,908 (Fitzgerald etal.) and U.S. Pat. No. 4,878,378 (Harada) are concerned with systemsthat measure apparent viscosities for process controls. U.S. Pat. No.6,393,898 (Hajduk et al.) describes a system that measures many testliquids simultaneously. These viscometers measure apparent viscosities.However, because of the non-universality of the apparent viscositymeasurement, a correlation of the apparent viscosity of a specificsample measured with a specific method with the true viscosity has to befound separately when desired. Fundamental development of formulationsfor materials requires the true viscosity measurement. Also the designsof processing equipment and accessories, such as dies, molds, extrusionscrews, etc., require the true viscosity of the materials. However, theapparent viscosity measurement has been used for a quick test as anindication since it is easier and faster to measure and often moreeconomical. The true viscosity is more difficult to get and can be onlymeasured with a few types of instruments: rheometers and capillaryviscometers. The rheometers impose a precise and known shear rate ontest samples, thereby measuring true viscosities. The rheometers areversatile and usually equipped to also measure other properties.Therefore they are usually expensive. Further, large amounts of samplesare usually required for viscosity measurement with a rheometer. Also,rheometers are not well suited for on-line applications. Circularcapillary viscometers can measure apparent and true viscositiesdepending on whether a proper compensation is taken into account. Thecapillary viscometer needs a pressure drop measurement along thecapillary for viscosity. Since the capillary is circular incross-section, only pressure at the entrance and exit can be measured.Because of this limitation, the capillary viscometer measures onlyapparent viscosity unless the entrance effect is corrected for by usingtwo different capillaries with different length to diameter ratios.However, use of two capillaries makes the capillary viscometers bulkyand/or time consuming. Capillary viscometers are described in U.S. Pat.No. 6,575,019 (Larson); U.S. Pat. No. 4,920,787 (Dual et al.); U.S. Pat.No. 4,916,678 (Johnson et al.); and U.S. Pat. No. 4,793,174 (Yau).Microfluidic viscometers are disclosed in U.S. Pat. No. 6,681,616(Michael Spaid et al.) and Publication No. 2003/0182991 (Michael Spaidet al.). Residence time of a marker in a fluidic channel is used tomeasure the viscosity, which is not a true viscosity unless the testliquid is Newtonian. Only an apparent viscosity is measured fornon-Newtonian liquids. The portable viscometer disclosed in U.S. Pat.No. 5,503,003 (Brookfield) utilizes a well known torque measurement of aspindle rotating in a sea of liquid for viscosity measurement. Asindicated, and as is well known, this method only measures apparentviscosity.

In summary, most viscosity measurement techniques yield apparentviscosity and require relatively large volumes of sample. Also, theseinstruments require cleaning of the parts in contact with liquid(container, spindle, etc.) before the measurement of the next sample.Such a cleaning is time consuming so that viscosity measurementstypically take about 30 minutes from the set-up to the test. The largersample volume requirement with current techniques also increases thecleaning time and waste. Therefore, there is no genuine portableviscometer which measures true viscosity for samples in small quantityand in a fast manner. The slit viscometer disclosed in my U.S. Pat. No.7,290,441 makes it possible to measure the true viscosity of smallsamples. It requires, however, a precision liquid dispensing system andassociated electronics to provide and control the flow of liquid throughthe viscometer. A simple precision liquid dispensing system which isportable and can be use with a variety of samples is not disclosed inthe prior art.

SUMMARY

According to some embodiments, a portable viscosity measurementinstrument or viscometer includes a miniature viscosity measurementsensor, a portable precision liquid dispensing system for forcing aliquid sample through the miniature viscosity measurement sensor, acontroller for controlling operation of the viscometer, and a displayfor displaying the measured viscosity of the liquid. The sensor designis described in my Pat. Nos. 6,892,583 and 7,290,441, which are herebyincorporated by reference as if fully set forth herein. The portablesystem measures the true viscosity of a liquid and requires only smallvolume samples of the liquid for measurement. This application alsodescribes a fast and easy way to obtain samples of liquid to be testedand to insert the samples of liquid into the viscometer for testing.

The portable precision liquid dispensing system in accordance with someembodiments includes a positive displacement pump which operates inconjunction with a positive displacement sample container, which will bereferred to as a positive displacement pipette, in which the sample ofthe liquid for which the viscosity is to be measured is supplied. Thepipette may be removable from and replaceable in the viscometer so thata sample of liquid to be tested can be drawn into the pipette whenremoved and separate from the viscometer and the pipette with the sampleof liquid therein then inserted into the viscometer for measuring theviscosity of the sample of liquid in the pipette. The pipette includes aplunger that slides within the pipette to draw a sample into the pipette(this can be done by hand) and to force the sample from the pipette whenin the viscometer. In one embodiment of the positive displacement pump,a precision motor drives a lead screw which moves a push back in contactwith the pipette plunger when positioned in the viscometer. As the pushback moves the plunger in the pipette, liquid is dispensed from thepipette into a flow passage of the miniature viscosity measurementsensor. Control electronics control operation of the precision motor todispense the liquid to be tested from the pipette at a known flow rateinto the flow passage of the miniature viscosity measurement sensor.

The miniature flow-through viscosity measurement sensor includes amicron scale flow channel combined with a pressure sensor array whichmeasures the pressure drop of a fully developed flow of the liquid inthe flow channel. In some embodiments, when a velocity field of a flowreaches a steady state (through a transition from an entrance of theflow channel), the flow is deemed to be fully developed. In someembodiments, a fully developed flow of the liquid has a same velocityprofile along a length of the flow channel. For example, a velocity of afully developed flow of the liquid at a center of the flow channel neara first end of the flow channel is identical to a velocity of the fullydeveloped flow of the liquid at a center of the flow channel near asecond end, opposite to the first end, of the flow channel. The pressuredrop is proportional to the shear stress of the liquid flowing throughthe channel. The shear rate is proportional to flow rate. Viscosity ofthe sample liquid is calculated by dividing the shear stress by theshear rate. The resulting measurement of viscosity can be shown in adisplay. Microcontroller or microprocessor based electronics can formthe controller electronics (also called herein an electronic controller)of the viscometer to control the motor of the pump and process the datafrom the pressure sensors. The processed data can be displayed and mayalso be stored and/or sent to remote devices.

In some embodiments, if temperature control of the sample is desired,the viscometer, the viscosity sensor, and/or the sample in the pipettemay be conditioned to a set temperature with a Peltier based temperaturecontrol device or other generally accepted temperature control means.

In some embodiments, the viscometer is configured to store a history ofmeasured viscosity values for various uses and/or may store a databaseof the known viscosity values of various liquids, such as liquidsfrequently expected to be measured. This allows a quick comparison ofthe known viscosity of a known liquid with the measured viscosity of asample thought to be the known liquid. Discrepancies between the knownvalue and the measured value can indicate that the test liquid is notthe liquid it is thought to be or can indicate problems with theviscometer so that the viscometer can be checked.

In accordance with some embodiments, a viscometer includes a viscositysensor with a liquid flow channel and at least two pressure sensorspositioned along the liquid flow channel and configured to measure apressure drop of a liquid flowing through the liquid flow channel. Theviscometer also includes a dispensing mechanism configured to causedispensing of a liquid from the syringe to the viscosity sensor at aknown flow rate; and an electronic controller configured to controloperations of the dispensing mechanism and receive and process data fromthe viscosity sensor.

In some embodiments, the dispensing mechanism is configured to couplewith a syringe, and the syringe is coupled with the viscosity sensor andconfigured to contain a liquid.

In some embodiments, the viscometer includes a sample loading interfacethrough which the viscometer is configured to receive the liquid. Insome embodiments, the syringe includes the sample loading interface. Insome embodiments, the sample loading interface includes a selection orswitching valve (as used herein, the term “selection valve” is usedthroughout to represent wide ranges of valves) coupled with theviscosity sensor and the syringe and located between the viscositysensor and the syringe.

In some embodiments, the viscometer includes a transporting deviceconfigured to couple with the syringe and the dispensing mechanism. Thetransporting device is configured to move the syringe between a firstlocation for aspirating a test liquid into the syringe and a secondlocation for coupling the syringe to the viscosity sensor, wherein thesecond location is distinct from the first location and the transportingdevice is configured to move the syringe between the first location andthe second location independent of user intervention.

In some embodiments, the viscometer is configured to aspirate the testliquid into the syringe independent of user intervention.

In some embodiments, the viscometer includes a viscosity sensor modulethat includes a plurality of viscosity sensors.

In some embodiments, a plurality of liquid flow channels is defined inthe viscosity sensor and at least two pressure sensors are positionedalong each of two or more liquid flow channels of the plurality ofliquid flow channels.

In some embodiments, the viscometer includes a temperature controldevice. In some embodiments, the temperature control device is coupledwith the electronic controller and the electronic controller isconfigured to control the temperature control device. In someembodiments, the viscosity sensor is temperature controlled. In someembodiments, the syringe is temperature controlled.

In some embodiments, the electronic controller is configured todetermine viscosity values of the liquid at a plurality of temperatures,the liquid including proteins of a first type; and determine a meltingtemperature of the proteins of the first type from viscosity values ofthe liquid at the plurality of temperatures.

In some embodiments, the electronic controller is configured to:determine viscosity values of a second liquid at a plurality oftemperatures, the second liquid including proteins of a second type; anddetermine a melting temperature of the proteins of the second type fromviscosity values of the second liquid at the plurality of temperatures.

In some embodiments, the viscometer includes a mixer coupled with theelectronic controller and configured to mix the liquid with a solvent toobtain a mixed solution. A concentration of a solute in the mixedsolution is distinct from a concentration of the solute in the liquid.The electronic controller is configured to: measure a viscosity of themixed solution; and initiate repeated mixing and measuring to obtainviscosity values of the mixed solution for a plurality of concentrationsof the solute.

In some embodiments, the viscometer includes a sample injector. Thesample injector is configured to dispense a continuous stream of liquidsto the viscosity sensor. The continuous stream of liquids includes twoor more batches of test liquids. Any two adjacent batches of testliquids, of the two or more batches of test liquids, are separated by atleast one inert liquid immiscible with the two adjacent batches of testliquids.

In some embodiments, the viscometer includes a pump configured todispense a cleaning solution through the liquid flow channel of theviscosity sensor.

In some embodiments, the viscometer is configured to couple with asource of gas and provide the gas through the liquid flow channel.

In some embodiments, the gas is regulated dry gas.

In some embodiments, the viscometer is configured to determine anoperation status of the viscosity sensor based on one or moremeasurements for the regulated dry gas.

In some embodiments, the viscometer is configured to self-calibrate byusing a preselected reference liquid.

In some embodiments, the viscometer includes one or more of: a pH meter,a density meter, and a conductivity meter.

In some embodiments, the liquid flow channel comprises a rectangularliquid flow channel.

In some embodiments, the viscosity sensor has an inlet and an outlet,the inlet configured to couple with a syringe, and the viscometerfurther comprises a positive pressure source coupled with the outlet ofthe viscosity sensor.

In accordance with some embodiments, a method for performing a viscositymeasurement includes receiving, at a viscometer comprising a viscositysensor with a liquid flow channel, a liquid from a syringe into theliquid flow channel at a known flow rate. The viscometer furthercomprises a dispensing mechanism and an electronic controller. At leasttwo pressure sensors are positioned along the liquid flow channel andconfigured to measure a pressure drop of the liquid flowing through theliquid flow channel. The electronic controller is configured to controloperations of the dispensing mechanism and receive and process data. Thedispensing mechanism is configured to couple with the syringe and causedispensing of a liquid in the syringe to the viscosity sensor at theknown flow rate. The method also includes measuring a viscosity of theliquid.

In accordance with some embodiments, a method for performing a viscositymeasurement includes moving a syringe between a first location foraspirating a test liquid into the syringe and a second location forcoupling the syringe with a viscosity sensor of a viscometer independentof user intervention. The second location is distinct from the firstlocation. The method also includes coupling a syringe with the viscositysensor. The viscosity sensor is with a liquid flow channel. The methodfurther includes receiving, at the viscometer, a liquid from the syringeinto the liquid flow channel at a known flow rate. The viscometerfurther comprises a dispensing mechanism and an electronic controller.At least two pressure sensors are positioned along the liquid flowchannel and configured to measure a pressure drop of the liquid flowingthrough the liquid flow channel. The electronic controller is configuredto control operations of the dispensing mechanism and receive andprocess data. The dispensing mechanism is configured to couple with thesyringe and cause dispensing of a liquid in the syringe to the viscositysensor at the known flow rate. The viscometer further comprises a sampleloading interface through which the viscometer is configured to receivethe liquid, wherein the syringe includes the sample loading interface.The method includes measuring a viscosity of the liquid.

BRIEF DESCRIPTION OF THE DRAWINGS

Additional features and advantages will be apparent from the detaileddescription which follows, taken in conjunction with the accompanyingdrawings, which together illustrate, by way of example, features ofexemplary embodiments.

FIG. 1 is a schematic representation of a portable viscometer inaccordance with some embodiments.

FIG. 2A is a schematic representation of a flow-through viscosity sensorin accordance with some embodiments.

FIG. 2B is a schematic cross-sectional representation of a flow-throughviscosity sensor in accordance with some embodiments.

FIG. 2C is a schematic cross-sectional representation of a flow-throughviscosity sensor in accordance with some embodiments.

FIG. 3 is a cross-sectional view of a pipette useable in the system inaccordance with some embodiments, showing the pipette plunger in anintermediate position in the pipette.

FIG. 4 is a similar cross-sectional view of the pipette of FIG. 3 inaccordance with some embodiments, showing the pipette plunger inposition before a sample of liquid has been drawn into the pipette orafter the sample of liquid has been dispensed from the pipette.

FIG. 5 is a schematic representation of a portable viscometer inaccordance with some embodiments.

FIG. 6A is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 6B is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 6C is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 6D is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 6E is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 7 is a chart that illustrates a method of determining a meltingtemperature in accordance with some embodiments.

FIGS. 8A-8C are flow charts representing a method of measuring aviscosity of a liquid in accordance with some embodiments.

Reference will now be made to the exemplary embodiments illustrated, andspecific language will be used herein to describe the same. It willnevertheless be understood that no limitation of the scope of the claimsis thereby intended.

DESCRIPTION OF EXAMPLE EMBODIMENTS

In accordance with some embodiments, an improved viscometer, which isportable, easier-to-use, more accurate, and a faster way of measuringthe viscosities of liquid samples than prior art viscometers, isdescribed. Referring to FIG. 1, the viscometer 22 includes a precisionpump, indicated generally by reference number 20, a liquid container 14for supplying a sample of the liquid for which a viscosity measurementis desired, a flow-through viscosity sensor 15, a controller 18, and adisplay 19.

The pump 20 works in conjunction with a sample container shown andreferred to as a pipette 14 having a pipette barrel or body 13 and aplunger 12 slidably positioned in the pipette barrel 13 with plunger endportion 24 extending from an end of the barrel 13. The pipette 14 may beremovably positioned and held in the viscometer by a mounting mechanism28 so the pipette can be removed, filled with a sample of liquid to betested, and replaced into the mounting mechanism of the viscometer, orcan be removed and replaced with another similar pipette containing asample of liquid to be tested. The pipette may be made disposable so anew, clean pipette is used for each sample of liquid. The pump includesa precision motor 23, a lead screw 10 rotatable by the motor 23 througha drive mechanism 26, such as a gear drive or belt drive, and a pushback 11 mounted on lead screw 10 which contacts the end 25 of pipetteplunger end portion 24 when pipette 14 is positioned in the viscometer.The push back 11 moves laterally along lead screw 10 in response to therotation of the lead screw 10 by motor 23.

An example of a pipette construction is shown in FIGS. 3 and 4. Apipette plunger 41 has a plunger head 42 sealingly and slidably receivedin pipette barrel 40 with an end portion 45 extending from an end of thepipette barrel 40. Both the pipette barrel and pipette plunger can befabricated from plastic by injection molding. The plunger can slide backand forth inside of the barrel 40. In order to minimize air entrapmentwhen filling the pipette with sample liquid, the end of plunger head 42is shaped to closely fit into liquid flow barrel end 43, as shown inFIG. 4, to minimize any air gap 44 between the two. With the pipette inthe condition shown in FIG. 4, the liquid flow end 43 of the pipette canbe inserted into a liquid for which the viscosity is to be determined. Auser can grasp the end portion 45 of the plunger 41 extending from thepipette barrel 40 and pull the plunger back from the end 43 of thepipette barrel to draw sample into the pipette barrel through an openingin barrel end 43. FIG. 3 shows the plunger 41 pulled back from thebarrel end to create space 46 in the pipette barrel which will containthe liquid sample drawn into the pipette. As the pipette plunger 41continues to be pulled back in pipette barrel 40, sample will continueto be drawn into the increasing space 46. The user stops pulling backthe plunger 41 when the desired amount of sample is drawn into thepipette barrel. If the plunger 41 is pushed toward the liquid flow end43 of the barrel 40, fluid in space 46 is discharged from the barrel 40though the opening in barrel end 43.

Flow-through viscosity sensor 15 includes a liquid inlet connector 16and a liquid outlet connector 21. As shown in FIG. 1, the liquiddischarged from the end of the pipette barrel 13 is coupled throughliquid inlet connector 16 to a liquid entrance to the viscosity sensor15. A liquid discharge tube 17 is coupled through the liquid outletconnector 21 to guide liquid away from a liquid exit of viscosity sensor15.

FIG. 2A illustrates a perspective view of the flow-through viscositysensor 15 in accordance with some embodiments. Also shown in FIG. 2A areplanes AA and BB, which are drawn to facilitate the understanding ofFIGS. 2B and 2C.

FIG. 2B is a cross-sectional view of the flow-through viscosity sensor15 along the plane AA (shown in FIG. 2A) in accordance with someembodiments.

Referring to FIG. 2B, the flow-through viscosity sensor 15 includes aliquid flow channel 31, with a flow channel entrance 35 and flow channelexit 36 formed in a channel substrate 39. The flow channel 31 has arectangular cross-section with the channel substrate 39 providing threesides of flow channel 31, leaving one open side. A monolithic sensorplate 38 formed by a pressure sensor membrane 37 and a pressure sensorsubstrate 30 is combined with the channel substrate 39 to close the openside of flow channel 31. Monolithic sensor plate 38 provides a pluralityof independent pressure sensors and is positioned with respect to thechannel substrate 39 to locate at least two independent pressure sensorsalong the flow channel 31 spaced sufficiently away from the channelentrance 35 and channel exit 36 whereby a pressure drop of fullydeveloped flow of liquid through the flow channel 31 can be measured bythe pressure sensors. As explained above, the pressure drop isproportional to the shear stress of the liquid flowing through thechannel. The shear rate is proportional to the flow rate. Viscosity ofthe sample liquid is calculated by dividing the shear stress by theshear rate.

In the embodiment shown in FIG. 2B, three independent pressure sensorsare provided by the monolithic sensor plate 38 along flow channel 31.Each of the independent pressure sensors is formed by a cavity 33 in thepressure sensor membrane 37. The portions 34 of the pressure sensormembrane 37 that extend over the respective cavities 33 will deflectinto the respective cavities 33 upon application of pressure to suchportions 34 of the pressure sensor membrane extending over therespective cavities 33. The amount of deflection into a respectivecavity is proportional to the pressure applied by the liquid flowing inthe flow channel 31 to the pressure sensor membrane over the respectivecavities.

A detector is provided in each of the cavities for detecting thedisplacement of the membrane into the respective cavity which provides ameasurement of the pressure applied to the membrane over the cavity.Various detectors can be used, such as a capacitance detector whereinone capacitor electrode is located on the pressure sensor membrane overa cavity and the other capacitor electrode is located on the sensorsubstrate 30 covering the cavity. Displacement of the membrane moves thecapacitor electrodes closer together and changes the capacitance whichprovides the measure of pressure. It will be noted that the surface ofthe pressure sensor membrane 37 along the liquid channel 31 issubstantially a smooth continuous surface without individual pressuresensors being inserted into the surface to form irregularities anddiscontinuities. This smooth channel surface is important to obtainingaccurate pressure measurements. A more detailed description of thepressure sensor and variations and different embodiments of the pressuresensor construction and of the flow-through viscosity sensor areprovided in U.S. Pat. Nos. 6,892,583 and 7,290,441, which areincorporated by reference herein in their entireties. Liquid inletconnector 16 attached to channel substrate 39 around liquid channelentrance 35 provides for connection of a source of pressurized sampleliquid, here liquid discharged from pipette 14, and liquid outletconnector 21 attached to channel substrate 39 around liquid channel exit36 provides for connection to a sample liquid drain or holdingreservoir.

FIG. 2C is a cross-sectional view of the flow-through viscosity sensor15 along the plane BB (shown in FIG. 2A) in accordance with someembodiments. As illustrated in FIG. 2C, in some embodiments, a pluralityof liquid flow channels is defined in the viscosity sensor. In someembodiments, at least two pressure sensors are positioned along each oftwo or more liquid flow channels of the plurality of liquid flowchannels. In some other embodiments, only a single liquid flow channelis defined in the viscosity sensor.

In some embodiments, a plurality of viscosity sensors is formed on asingle substrate, and the single substrate defines a plurality ofchannels for the plurality of viscosity sensors. In some embodiments,each viscosity sensor of a plurality of viscosity sensors is formed on arespective substrate.

Referring back to FIG. 1, controller 18 includes one or moremicrocontrollers or microprocessors, and other electrical and electroniccomponents for controlling operation of the viscometer and peripheralcomponents, for performing calculations, for controlling the display 19which can display the measured viscosity and other information such asstatus of the viscometer, and for communicating with and transferringdata to other equipment such as other computers. Communication can bethrough ports such as RS232 or USB ports or can be through wireless orother communication means. Controller 18 will generally includeinterface means, such as a keyboard, touch button pad or key pad, anexternal computer, or other data entry means such as buttons, a mouse,or a touch screen in display 19, whereby a user can enter control andother instruction and information into the controller.

To measure the viscosity of a sample of liquid, a sample of the liquidfor which the viscosity is to be determined is obtained in a liquidsample holding pipette. The sample of liquid in the pipette can havebeen withdrawn from a source of the liquid into the pipette by the userof the viscometer or can be otherwise supplied to the user of theviscometer in the pipette. As shown in FIG. 1, the pipette 14 is mountedin the viscometer 22 and is held in position in the viscometer bymounting mechanism 28. The controller is then activated to control theviscometer to make a viscosity measurement. The controller will operatethe motor 23 to advance the push back 11 to a position as shown in FIG.1 against the end 25 of the pipette plunger. Alternatively, the pushback 11 could be positioned, such as manually, by the user when thepipette is mounted in the viscometer prior to activation of thecontroller.

With the push back 11 in position against the end 25 of the pipetteplunger, the controller controls the motor 23 so as to rotate lead screw10 to advance the push back 11 and pipette plunger 12 at a desired speedor speeds to discharge the liquid from the pipette at a known desiredflow rate or flow rates. As the plunger moves, the liquid is forced fromthe pipette into the viscosity sensor 15 and flows through the flowchannel 31 in which the pressure drop of a fully developed flow of theliquid is measured by the pressure sensors of the monolithic pressuresensor 38. The pressures are measured as the local pressures overrespective membrane portions of the pressure sensors along the flowchannel 31 deflect sensor membrane portions 34 into respective cavities33. The pressure drop measured along the flow channel 31 (the differencein pressures measured between successive pressure sensors along the flowchannel) is proportional to the viscosity of the liquid at the specificflow rate. If the sample viscosity varies with the flow rate, then thecontrol can be instructed to dispense the liquid at different flow ratesin sequence, with or without flow stoppage. When the pressure values areacquired and the viscosity values calculated as a function of flow rate,the relationship is corrected for non-Newtonian viscosity in a knownmanner. The measured viscosities may be displayed on the display 19, maybe stored in a controller memory or auxiliary memory, and/or transmittedto a remote memory or computer.

As the liquid is injected into liquid flow channel 31 in the viscositysensor 15 at an initially set flow rate (or shear rate), the viscometersenses the pressure inside the liquid flow channel 31. The controllercan be programmed to determine if the pressure level is optimal for thehighest accuracy or assured accuracy of the viscosity measurement. Ifthe pressure level is too low, the controller determines and sets thenext flow rate value and ramps up the flow rate to the new set value.The controller continues the iteration to reach the optimal flow ratefor the particular viscosity measurement. In this way, viscosity ofunknown liquids can be accurately and automatically measured.

When the viscosity measurement or measurements for a sample of liquidhave been obtained, the push back 11 is operated to move it back to aposition to allow the used pipette to be removed and a new pipette witha sample of new liquid therein for testing to be inserted in theviscometer. The pipette with the sample of new liquid to be tested maybe a new disposable pipette or a reloaded used pipette. For the newviscosity measurement, the controller operates the viscometer asdescribed above to determine the viscosity of the sample of new liquid.In this test, the liquid from the new sample displaces the liquid fromthe old sample in the viscosity sensor 15. In this way, no cleaning ofthe viscosity sensor is needed. If the two successive liquids to betested are not compatible or miscible, then the viscosity sensor 15needs to be cleaned with a cleaning liquid compatible to both liquids tobe tested prior to dispensing the new liquid into the viscosity sensor15. This cleaning can be done by loading a pipette containing thecleaning liquid into the viscometer and operating the viscometer toforce the cleaning liquid through the viscosity sensor 15 between thetwo liquids being tested.

The viscometer 22 may be powered by a battery, such as a rechargeablebattery, so that it is truly portable, or may be powered by connectingit to a source of power as it is moved from place to place.

In some instances it may be desirable to control the temperature of theliquid for which the viscosity is being measured. If temperature controlis desired, the viscometer 22, the viscosity sensor 15, and/or thesample in the pipette 14 may be conditioned at a set temperature with aPeltier based temperature control device or other generally acceptedtemperature control means. For example, as shown in FIG. 5, which issimilar to FIG. 1, a temperature control device 50 may be placed in orin contact with pipette mounting mechanism 28 so as to heat or cool aliquid sample holding pipette 14 and the liquid sample contained thereinwhen the pipette is mounted in the mounting mechanism 28. Depending uponhow the temperature control device 50 is mounted in pipette mountingmechanism 28, the pipette mounting mechanism may also be heated orcooled to the set temperature. Some time may be required for the samplein the pipette to reach the set temperature. Similarly, a temperaturecontrol device 52 may be placed in or in contact with the viscositysensor 15 so as to heat or cool and maintain the temperature of thematerial forming flow channel 31 of the viscosity sensor 15 at the settemperature. This will tend to maintain the material flowing through theflow channel 31 at substantially the set temperature. As indicated, thetemperature control devices may be Peltier devices or other knowntemperature control devices. Further, temperature sensors can bepositioned to measure the temperature of the sample liquid at variouslocations in the viscometer. For example, a temperature sensor can beincluded at one or more locations in the sensor membrane 37 along theflow channel 31 as shown in my prior referenced patents. Rather thanseparately controlling the temperature of separate components of theviscometer 22 as described above, the viscometer 22, or the partsthereof to be temperature controlled, may be mounted in a housing wherethe temperature within the housing, and thus the temperature of theentire viscometer or the parts thereof in the housing, are togethertemperature controlled.

As indicated in my prior referenced patents, the flow-through viscositysensor described is very small, generally constructed of semiconductormaterials or other materials used in microfabrication processes. Forexample, the pressure sensor membrane may be a portion of a siliconwafer, while the pressure sensor substrate and the channel substrate maybe portions of a borosilicate glass wafer. The flow channel typicallycan be as small as about ten micrometers in width and about onemicrometer in depth, with a length as short as about one hundredmicrometers. Thus, the flow-through viscosity sensor is very small andsmall sample sizes can be used in determining viscosity. This small sizeof the flow-through viscosity sensor and the small amount of sampleneeded for viscosity testing means that the other viscometer components,such as the pipettes and the pump can also be made relatively small sothe viscometer can easily be made as a relatively small portable unit.

Rather than making a portable viscometer, the same viscometerconstruction can be used to provide a stationary viscometer wheresamples of liquid to be tested can be collected from different locationsin different pipettes and then transported to the viscometer and testedat the location of the viscometer.

If desired, a database of published or otherwise known viscosity valuesfor liquids frequently measured or that might be measured can be storedin a memory in the viscometer controller. With such a databaseavailable, a user can easily display a known viscosity value from thedatabase for a selected liquid and compare it to the viscosity valuemeasured for a sample liquid thought to be the known liquid.Discrepancies between the published value and the measured value canindicate that the test liquid is not the liquid it is thought to be orcan indicate problems with the viscometer so that the viscometer can bechecked. In addition, for various reasons, it may be advantageous for auser from time to time to have access to the known viscosity values ofparticular liquids other than the liquid being tested at that time.Further, the viscometer may store a history of measured viscosity valueswith appropriate identification, again which may be used by the user ofthe viscometer for various purposes. For example, with such a history ofmeasured viscosity values, a user can compare the viscosity of a liquidcomponent being used in a manufacturing process at different times toensure that the liquid component is within specifications required forthe liquid component, or can determine and correlate a viscosity valueof the component with particular desired attributes of the resultingproduct.

While the illustrated embodiment of the pump is shown and described insome embodiments as including a motor, lead screw, and push back to movethe plunger in the pipette, various other means of moving the plunger inthe pipette or of providing a precision discharge of sample liquid froma sample container can be used.

FIG. 6A is a schematic representation of a viscometer in accordance withsome embodiments.

FIG. 6A illustrates that a viscometer includes a viscosity sensor module610. In some embodiments, the viscosity sensor module 610 includes asingle viscosity sensor. In some embodiments, the viscosity sensormodule 610 includes a plurality of viscosity sensors. In someembodiments, a viscosity sensor has a liquid flow channel and at leasttwo pressure sensors. The at least two pressure sensors are positionedalong the liquid flow channel (e.g., a first pressure sensor located atan upstream location in the liquid flow channel and a second pressuresensor located at a downstream location in the liquid flow channel) andconfigured to measure a pressure drop of a liquid flowing through theliquid flow channel.

As illustrated in FIG. 6A, the viscometer also includes a dispensingmechanism 630 (e.g., the precision pump 20, FIG. 1). In someembodiments, the dispensing mechanism 630 is configured to couple with asyringe 620 (e.g., a pipette). In some embodiments, the dispensingmechanism 630 is configured to removably couple with the syringe 620.The dispensing mechanism 630 is configured to cause dispensing of aliquid from the syringe 620 to the viscosity sensor at a known flowrate. In some embodiments, the syringe 620 is coupled with the viscositysensor. In some embodiments, the syringe 620 is removably coupled withthe viscosity sensor.

FIG. 6A also illustrates that the viscometer includes an electroniccontroller 660 configured to control operations of the dispensingmechanism 630 and receive and process data from the viscosity sensormodule 610 (or one or more viscosity sensors in the viscosity sensormodule 610).

In some embodiments, the dispensing mechanism 630 comprises anautosampler. In some embodiments, the autosampler is configured tocollect liquid samples from a plurality of containers (e.g., tubes,vials, or well in a plate) and sequentially dispense the collectedliquid samples (e.g., dispensing a first liquid sample from a firstcontainer, followed by dispensing a second liquid sample from a secondcontainer, etc.).

In some embodiments, the viscometer includes a selection valve 650. Insome embodiments, the selection valve 650 is coupled with an inlet ofthe viscosity sensor module 610 (or a viscosity sensor in the viscositysensor module 610) at one end and is coupled with the syringe 620 atanother end. Typically, the selection valve 650 is located between theviscosity sensor module 610 and the syringe 620. In some embodiments,the selection valve 650 is configured to receive one or more of a gasand a liquid from one or more sources other than the syringe 620. Thisis described below with respect to FIGS. 6C and 6E. In some embodiments,the electronic controller 660 is configured to control operations of theselection valve 650.

In some embodiments, the electronic controller 660 is configured tostore predetermined viscosity values of preselected liquids (e.g., in anon-volatile memory of the electronic controller 660 or in a separatestorage device that is located in the viscometer or remotely from theviscometer). In some embodiments, the predetermined viscosity values ofthe preselected liquids are used to identify a liquid, viscosity ofwhich is measured by the viscometer.

In some embodiments, the viscometer also includes an outlet module 670.The outlet module 670 is coupled with an outlet of the viscosity sensormodule 610 (or an outlet of a viscosity sensor in the viscosity sensormodule 610). In some embodiments, the outlet module 670 is coupled withone or more outlets of viscosity sensors in the viscosity sensor module610.

FIG. 6B is a schematic representation of a viscometer in accordance withsome embodiments. The viscometer illustrated in FIG. 6B includes theviscosity sensor module 610, the dispensing mechanism 630, and theelectronic controller 660, which are described above with respect toFIG. 6A. In some embodiments, certain features described above withrespect to FIG. 6A are applicable to FIG. 6B. For brevity, thesefeatures are not repeated herein.

FIG. 6B illustrates that, in some embodiments, the viscosity sensormodule 610 includes a viscosity sensor 612. FIG. 6B also illustratesthat, in some embodiments, the viscosity sensor module 610 includes asample preconditioner 614.

In some embodiments, the sample preconditioner 614 includes atemperature control device (e.g., a thermoelectric device, inparticular, a solid-state thermoelectric device such as a Peltierdevice, which is configured for cooling, heating, or both). In someembodiments, the sample preconditioner 614 is configured to control atemperature of a sample liquid using the temperature control device. Insome embodiments, the sample preconditioner 614 includes a temperaturesensor to measure a temperature of the sample liquid.

In some embodiments, the viscosity sensor 612 in the viscosity sensormodule 610 is coupled with a temperature control device. The temperaturecontrol device coupled with the viscosity sensor 612 is configured tocontrol a temperature of the viscosity sensor 612. In some embodiments,the viscosity sensor 612 is coupled with a temperature sensor. In someembodiments, the viscosity sensor module 610 is coupled with atemperature control device. The temperature control device coupled withthe viscosity sensor module 610 is configured to control a temperatureof the viscosity sensor module 610. In some embodiments, the viscositysensor module 610 is coupled with a temperature sensor. In someembodiments, the syringe 620 is coupled with a temperature controldevice. The temperature control device coupled with the syringe 620 isconfigured to control a temperature of the syringe 620. In someembodiments, the syringe 620 is coupled with a temperature sensor.

In some embodiments, the electronic controller 660 is configured toinitiate operations of one or more temperature control devices (e.g.,heating or cooling operations) described above. In some embodiments, theelectronic controller 660 is configured to receive temperatureinformation from one or more temperature sensors described above.

In some embodiments, the syringe 620 includes one or more of a barrel622 and a plunger 624 (also called a piston). For example, in someembodiments, the syringe 620 includes both the barrel 622 and theplunger 624 to dispense a liquid to a viscosity sensor. In someembodiments, the syringe 620 includes a barrel 622 through which aliquid is dispensed to a viscometer, without including a plunger 624.

In some embodiments, the dispensing mechanism 630 includes one or moreof an adapter 632, a motor 634, and a lead screw 636. In someembodiments, the lead screw 636 is coupled with the motor 634 and theadapter 632. For example, in some embodiments, a rotation of the motor634 initiates a rotation of the lead screw 636, which in turn initiatesa linear movement of the adapter 632 along a longitudinal direction ofthe lead screw 636. In some embodiments, the adapter 632 is configuredto mate with the plunger 624 of the syringe 620. In some embodiments,the adapter 632 is configured to releasably mate with the plunger 624 ofthe syringe 620. For example, in some embodiments, a rotation of themotor 634 initiates a linear movement of the plunger 624.

FIG. 6B also illustrates that, in some embodiments, the viscometerincludes a sample loading interface 626. In some embodiments, thesyringe 620 is coupled with the sample loading interface 626. In someembodiments, the syringe 620 includes the sample loading interface 626.In some other embodiments, the selection valve 650 includes the sampleloading interface 626. In some embodiments, the selection valve 650 iscoupled with the sample loading interface 626. In some embodiments, thedispensing mechanism 630 includes the sample loading interface 626. Insome embodiments, the dispensing mechanism 630 is configured to couplewith the sample loading interface 626. For example, in some embodiments,the dispensing mechanism 630 includes a peristaltic pump that initiatesdispensing of a liquid, received through the sample loading interface626, to a viscometer (e.g., through the syringe 620). In suchembodiments, the viscometer need not require a plunger (thus, in someembodiments, the syringe 620 does not include a plunger).

In some embodiments, the outlet module 670 includes one or more of: apositive pressure source 672, a pH meter 674, a conductivity meter 676,and a density meter 678. The pH meter 674 is configured to measure a pHof the liquid. As used herein, a pH refers to a measure of an acidity orbasicity of the liquid. The density meter 678 is configured to measure adensity of the liquid. The conductivity meter 676 is configured tomeasure a conductivity of the liquid. In some embodiments, the pH meter674 is configured to measure a pH of the liquid concurrently with ameasurement of a viscosity of the liquid (e.g., by a viscometer). Insome embodiments, the density meter 678 is configured to measure adensity of the liquid concurrently with a measurement of a viscosity ofthe liquid (e.g., by a viscometer). In some embodiments, theconductivity meter 676 is configured to measure a conductivity of theliquid concurrently with a measurement of a viscosity of the liquid(e.g., by a viscometer).

In some embodiments, the positive pressure source 672 includes a pump.In some embodiments, the pump is configured to provide a predefinedpressure to an outlet of the viscosity sensor module 610 (or theviscosity sensor 612 in the viscosity module 610). In some embodiments,the positive pressure source 672 includes a pressurized gas source(e.g., a pressurized gas tank, such as a nitrogen gas tank, or a pumpthat provides a pressurized air). In some embodiments, a pressureprovided to the outlet of the viscosity sensor module 610 by thepositive pressure source 672 causes a liquid in the viscosity sensormodule 610 (or the viscosity sensor 612 in the viscosity module 610) tomove toward the syringe 620. In some cases, applying a negative pressurefrom the syringe 620 (e.g., by pulling the plunger 624) to move a liquidin the viscosity sensor 612 to the syringe 620 damages pressure sensorsin the viscosity sensor 612 (e.g., in some cases, a vacuum created bythe suction from the syringe 620 damages the pressure sensors in theviscosity sensor 612). Thus, applying a positive pressure to the outletof the viscosity sensor 612 enables moving the liquid in the viscositysensor 612 to the syringe 620 without applying a negative pressure tothe viscosity sensor 612, thereby avoiding damages to the pressuresensors in the viscosity sensor 612. In some embodiments, both apositive pressure applied to the outlet of the viscosity sensor 612 anda negative pressure applied to the inlet of the viscosity sensor 612 areused to move the liquid in the viscosity sensor 612 to the syringe 620.In such embodiments, the negative pressure applied to the inlet of theviscosity sensor 612 is less than a negative pressure that is requiredat the inlet of the viscosity sensor 612 to move the liquid in theviscosity sensor 612 to the syringe 612 without application of apositive pressure to the outlet of the viscosity sensor 612, therebyreducing damages to the pressure sensors in the viscosity sensor 612.

In some embodiments, the provision of the pressure by the positivepressure source 672 is controlled by the electronic controller 660. Forexample, when the positive pressure source 672 includes a pump, theelectronic controller 660 is configured to control operations (e.g.,initiation and termination) of the pump. In another example, when thepositive pressure source 672 includes a pressurized gas source with acontrol valve, the electronic controller 660 is configured to controloperations (e.g., opening and closing) of the control valve. In someembodiments, the positive pressure source 672 includes a wastecontainer.

Liquids can be provided to the viscometer in multiple ways.

In some embodiments, a liquid is first provided into a syringe beforethe liquid is dispensed to the viscosity module 610. In someembodiments, the barrel 622 includes a side port through which thebarrel 622 is coupled with the sample loading interface 626. In someembodiments, the plunger 624 is moved to an end position, therebyallowing a sample loading through the sample loading interface 626 intothe barrel 622. Then, a liquid is injected into the barrel 622. In somecases, the injected liquid fills the syringe 620 (or the barrel 622 ofthe syringe 620). By moving the adaptor 632 of the dispensing mechanism630, the plunger 624 is moved to begin injection of the liquid to theviscosity sensor module 610. By controlling a speed of the adaptor 632(and hence a speed of the plunger 624), a flow rate and a shear rate ofthe liquid within the viscosity sensor 612 is controlled.

In some embodiments, the injected liquid is retrieved back to thesyringe 620. This is often desired if a volume of the liquid is limitedor if the liquid is to be reused. In this case, the plunger 624 ispulled by a movement of the adaptor 632. In some embodiments, thepositive pressure source 672 (or a positive pressure applied by thepositive pressure source 672) is used to facilitate retrieving of theinjected liquid. In particular, the positive pressure source 672 (or apositive pressure applied by the positive pressure source 672) greatlyincreases a speed of retrieving the injected liquid. Thus, in someembodiments, the injected liquid is retrieved back to the syringe 620 bya pressure applied by the positive pressure source 672. In someembodiments, the injected liquid is retrieved back to the syringe 620primarily by a pressure applied by the positive pressure source 672. Insome embodiments, the injected liquid is retrieved back to the syringe620 solely by a pressure applied by the positive pressure source 672.

In some embodiments, an autosampler 686 (FIG. 6B) is used to provideliquids to the viscometer. The autosampler 686 is configured to receivean array of vials or wells (e.g., wells in a 96 well plate). The arrayof vials or wells includes respective liquids for viscositymeasurements. The autosampler 686 is configured to aspirate a liquid ina vial or a well into an injector syringe 684 (which is distinct fromthe syringe 620 in some embodiments) and then move the injector syringe684 to the sample loading interface 626 to load the liquid to thesyringe 620. In some embodiments, the viscometer is coupled with liquidhandling equipment for testing many samples unattended. In someembodiments, the liquid handling equipment is configured to retrieve asample solution from vials in a tray or a well plate (e.g., 96-wellplate or 384-well plate).

In some embodiments, the syringe 620 and the dispensing mechanism 630are integral parts of the autosampler. The autosampler is configured toposition the syringe 620 for aspirating a liquid into the syringe 620,and to initiate loading the liquid into the syringe 620 using thedispensing mechanism 630. The autosampler is configured to, after theliquid is loaded into the syringe 620, move and position the syringe 620for dispensing the liquid into an inlet of the viscosity sensor module610, and initiate dispensing the liquid using the dispensing mechanism630 at a controlled flow rate for a viscosity measurement. In someembodiments, all these operations are controlled by the electroniccontroller. In some embodiments, one or more measured viscosity valuesare displayed. In some embodiments, these operations are fully automatedand repeated for multiple liquids, which increases a throughput ofviscosity measurements.

In some embodiments, a liquid is loaded through the selection valve 650positioned between the viscosity sensor module 610 and the syringe 620.In some embodiments, the selection valve 650 has more than two ports.For example, in some embodiments, a two-position three-port valve isused. A first port is coupled with the viscosity sensor module 610, asecond port is coupled with the syringe 620, and a third port is usedfor receiving liquids. When the valve is in a first position, the thirdport and the second port are fluidically connected (e.g., a liquidprovided into the third port flows into the syringe 620 through thesecond port) while the first port is fluidically disconnected (e.g., aliquid provided into the third port or a liquid in the syringe 620connected to the second port does not flow into the viscosity sensormodule 610). When the valve is in a second position, the first port andthe second port are fluidically connected (e.g., a liquid in the syringe620 connected to the second port flows into the viscosity sensor module610 connected to the first port) while the third port is fluidicallydisconnected (e.g., a liquid provided into the third port does not flowinto the viscosity sensor module 610 connected to the first port or thesyringe 620 connected to the second port). While the valve is in thefirst position, the plunger 624 is pulled to aspirate a liquid from thethird port to the syringe 620. In some embodiments, when an air gap isformed adjacent to an end of the plunger 624, additional liquid can beprovided through the sample loading interfaced 626 to remove the airgap. After the liquid is loaded into the syringe 620, the valve isswitched into the second position, thereby fluidically connecting thesyringe 620 and the viscosity sensor module 610. Then the dispensingmechanism 630 causes dispensing of the liquid at a controlled speed orshear rate into the viscosity sensor module 610 for viscositymeasurement.

In some embodiments, the syringe 620 includes a combination of injectionvalves. In some embodiments, the syringe 620 includes the combination ofinjection valves without the plunger 624 or the barrel. The combinationof injection valves facilitates semi-continuous testing of liquids. Insome embodiments, a liquid (also called herein a sample liquid) isprovided to a sample loop of the injection valves, followed by injectingthe liquid to a stream of liquids. In some embodiments, loading liquidsto the sample loop and injecting the liquids to the stream of liquidsare repeated. This repetition can enable semi-continuous viscositymeasurements.

In some embodiments, the sample liquid is surrounded by mobile eluent.In some embodiments, the mobile eluent is miscible with the sampleliquid. In some embodiments, the mobile eluent is immiscible with thesample liquid. For example, fluorocarbon is an excellent eluent. In someembodiments, the mobile eluent is provided by an immiscible liquidsource 682, which is described below with respect to FIG. 6C.

In some embodiments, a liquid is loaded into the syringe 620 directly,without using the sample loading interface 626. For example, in someembodiments, the syringe 620 is decoupled from the viscosity sensormodule 610 and one end of the syringe 620 (opposite to the plunger 624of the syringe 620) is inserted into a sample liquid. The sample liquidis loaded into the syringe 620 by retracting the plunger 624. Then thesyringe 620 is moved to couple with an inlet of the viscosity sensormodule 610. After the syringe 620 is coupled with the inlet of theviscosity sensor module 610, the sample liquid is injected for viscositymeasurement. In some embodiments, positioning and moving the positivesyringe up and down are utilized using a transporting device (e.g., arobotic arm in an autosampler).

The viscometer described herein can operate in a high pressureenvironment (e.g., a pressure as high as 30,000 psi if the pressuresensors in the viscosity sensor 612 are configured to detect only adifference between a pressure above a sensor membrane 33 (FIG. 2B) andbelow the sensor membrane 33. This can be achieved by forming a ventline 31 (FIG. 2B) below the sensor membrane (33). The vent lineequilibrates the pressures above (37, FIG. 2B) and below (33) themembranes under any pressure condition to which the viscosity sensor issubject. As the liquid flows through the flow channel (34, 35, 36, FIG.2B) at a controlled flow rate, viscosity of the liquid increases thepressure above the membrane (37). The pressure increment is measuredaccurately by the chip (39, FIG. 2B).

In some embodiments, a liquid in the syringe 620 is maintained under apreselected pressure. In some embodiments, the dispensing mechanism 630is maintained at a preselected pressure. This is significant, because,with a certain liquid, the viscosity of the liquid varies depending onthe pressure of the liquid. With such liquid, the liquid in the syringeneeds to be preserved at a desired pressure condition for accurateviscosity measurements. For example, viscosity of oil during anextraction process (e.g., from a deep well) is of great interest forpetroleum operations. Oil in a deep well is typically maintained at ahigh pressure (e.g., an in situ pressure in a deep well, which istypically at a pressure higher than an atmospheric pressure) during anextraction process. However, measuring the viscosity of the oil at a lowpressure (e.g., an atmospheric pressure) is inaccurate, because at thelow pressure, volatiles in the oil, dissolved in the oil under highpressure, evaporate and change the viscosity of the oil. This processcannot be reversed simply by re-pressurizing the oil to the highpressure after volatiles in the oil have evaporated. Thus, in suchapplication, the liquid in the syringe needs to be maintained at thepreselected pressure for accurate viscosity measurements.

FIG. 6C is a schematic representation of a viscometer in accordance withsome embodiments. The viscometer illustrated in FIG. 6C includes theviscosity sensor module 610, the dispensing mechanism 630, and theelectronic controller 660, which are described above with respect toFIGS. 6A and 6B. In some embodiments, certain features described abovewith respect to FIGS. 6A and 6B are applicable to FIG. 6C. For brevity,these features are not repeated herein.

The viscometer in FIG. 6C also includes the selection valve 650, whichis described above with respect to FIG. 6B.

In some embodiments, the selection valve 650 is coupled with a secondsyringe 680. In some embodiments, the viscometer includes the secondsyringe 680. In some embodiments, the syringe 620 is configured toprovide a first liquid, and the second syringe 680 is configured toprovide a second liquid. In some embodiments, the first liquid includesproteins of a first type, and the second liquid includes proteins of asecond type.

In some embodiments, the second syringe 680 is coupled with a seconddispensing mechanism 690. In some embodiments, the second syringe 680 iscoupled with the dispending mechanism 630 that is also coupled with thesyringe 620.

In some cases, viscosity of a mixture of liquids needs to be measured.In some embodiments, the liquids are mixed first off line before theviscosity of the mixture is measured. In some embodiments, theviscometer includes a mixer configured to mix multiple liquids on line.In some embodiments, the viscometer measures a viscosity of the mixtureas a function of concentration by adjusting a mixing ratio (e.g., aratio of flow rates of the liquids). In some embodiments, the mixingratio of the liquids is changed by changing pumping rates of one or moreliquids if external pumps are used to dispense the liquids. For example,a first liquid is a solvent and a second liquid is a solution of apolymer dissolved in the solvent at a high concentration. By varying themixing ratio, a viscosity of the mixture can be measured as a functionof a polymer concentration. In some embodiments, the mixture is injecteddirectly to an inlet of the viscosity sensor module 610. In some otherembodiments, the mixture is injected first to the syringe 620. In someembodiments, the selection valve 650 is used to mix liquids. Forexample, in some embodiments, the selection valve 650 includes amulti-port variable-flow-rate valve configured to adjust a ratio of flowrates of multiple liquids.

In some embodiments, the selection valve 650 is coupled with animmiscible liquid source 682. In some embodiments, the immiscible liquidsource 682 includes a pump and a reservoir configured to store animmiscible liquid. The immiscible liquid source 682 is configured toprovide a liquid that is immiscible with liquids in the syringe 620 andthe second syringe 680. For example, when the syringe 620 and the secondsyringe 680 include polar liquids (e.g., water), the immiscible liquidsource 682 is configured to provide a non-polar liquid. In someembodiments, the electronic controller 660 is configured to controloperations of the immiscible liquid source 682. In some embodiments, theelectronic controller 660 is configured to initiate providing animmiscible liquid between two liquid samples entering the viscositysensor module 610. Providing the immiscible liquid between two liquidsamples prevents mixing between the two liquid samples.

FIG. 6D is a schematic representation of a viscometer in accordance withsome embodiments. The viscometer illustrated in FIG. 6D includes theviscosity sensor module 610, the dispensing mechanism 630, and theelectronic controller 660, which are described above with respect toFIGS. 6A and 6B. FIG. 6D also illustrates the syringe 620, which isdescribed above with respect to FIGS. 6A and 6B. In some embodiments,the viscometer includes the selection valve 650, which is describedabove with respect to FIGS. 6A-6C. In some embodiments, certain featuresdescribed above with respect to FIGS. 6A-6C are applicable to FIG. 6D.For example, in some embodiments, the viscometer illustrated in FIG. 6Dincludes one or more of: the second syringe 680 (FIG. 6C) and the seconddispensing mechanism 690 (FIG. 6C). For brevity, these features are notrepeated herein.

In FIG. 6D, the viscometer also includes a transporting device 692,which is configured to couple with the syringe 620 and the dispensingmechanism 660. In some embodiments, the transporting device 692 isconfigured to move the syringe 620 between a first location foraspirating a test liquid into the syringe 620 (e.g., the location of thesyringe 620 shown in FIG. 6D) and a second location for coupling thesyringe 620 to the viscosity sensor module 610 (or a viscosity sensor inthe viscosity sensor module 610) (e.g., the location of the syringe 620shown in FIG. 6B). As illustrated in FIGS. 6B and 6D, the secondlocation (for coupling the syringe 620 to the viscosity sensor module610, FIG. 6B) is distinct from the first location (for aspirating a testliquid into the syringe 620, FIG. 6D). In some embodiments, thetransporting device 692 is configured to move the syringe 620 betweenthe first location and the second location independent of userintervention (e.g., without a manual input from a user). In someembodiments, the electronic controller 660 is configured to controloperations of the transporting device 692.

In some embodiments, the syringe 620, when positioned at the firstlocation, is in contact with the test liquid in a test liquid container696 (e.g., a vial, tube, bottle, etc.). In some embodiments, thedispensing mechanism 630 is activated to initiate aspirating the testliquid into the syringe 620 (e.g., by pulling back a plunger of thesyringe 620).

In some embodiments, the transporting device 692 includes a robotic arm.In some embodiments, the transporting device 692 includes one or morerotary joints. In some embodiments, the transporting device 692 includesone or more rails 694. In some embodiments, the transporting device 692includes a belt and pulley mechanism for moving the syringe 620 betweenthe first location and the second location. In some embodiments, theelectronic controller 660 is configured to control the transportingdevice 692.

FIG. 6E is a schematic representation of a viscometer in accordance withsome embodiments. The viscometer illustrated in FIG. 6E includes theviscosity sensor module 610, the dispensing mechanism 630, and theelectronic controller 660, which are described above with respect toFIGS. 6A and 6B. FIG. 6D also illustrates the syringe 620, which isdescribed above with respect to FIGS. 6A and 6B. In some embodiments,the viscometer includes the selection valve 650, which is describedabove with respect to FIGS. 6A-6C. In some embodiments, certain featuresdescribed above with respect to FIGS. 6A-6D are applicable to FIG. 6E.For example, in some embodiments, the viscometer illustrated in FIG. 6Eincludes the transporting device 692 (FIG. 6D). In another example, insome embodiments, the viscometer illustrated in FIG. 6E includes thesecond syringe 680 (FIG. 6C) and the second dispensing mechanism 690(FIG. 6C). For brevity, these features are not repeated herein.

In some embodiments, the selection valve 650 is coupled with one or moreof: a cleaning solution source 697, a gas source 698, and a referenceliquid source 699. In some embodiments, at least one of the cleaningsolution source 697, the gas source 698, and the reference liquid source699 includes a pump and a reservoir configured to store a respective gasor liquid.

In some embodiments, the cleaning solution source 697 is configured toprovide a cleaning solution. For example, in some embodiments, thecleaning solution source 697 provides the cleaning solution to theselection valve 650 to clean the selection valve 650. In someembodiments, the cleaning solution source 697 provides the cleaningsolution to clean the viscosity sensor module 610 (or a viscosity sensorin the viscosity sensor module 610, and in particular, a liquid flowchannel of the viscosity sensor). In some embodiments, the cleaningsolution source 697 provides the cleaning solution to clean the syringe620. In some embodiments, a miscible and volatile solution is used as acleaning solution, thereby enabling faster evaporation of the cleaningsolution.

In some embodiments, the gas source 698 is configured to provide a gas.In some embodiments, the gas provided by the gas source 698 is a dry gas(e.g., dry nitrogen and clean dry air, such as −100° F. dew point air).In some embodiments, the gas source 698 provides the gas to theselection valve 650 to dry the selection valve 650. For example, anyremaining liquid (e.g., a cleaning solution) is dried with the gas. Insome embodiments, the gas source 698 provides the gas to dry theviscosity sensor module 610 (or a viscosity sensor in the viscositysensor module 610). In some embodiments, the gas source 698 provides thegas to dry the syringe 620.

In some embodiments, the reference liquid source 699 is configured toprovide a reference liquid. In some embodiments, the reference liquid isa liquid of a known viscosity (e.g., under one or more measuringconditions, such as at one or more temperatures). In some embodiments,the reference liquid source 699 provides the reference liquid to theviscosity sensor module 610 (or a viscosity sensor in the viscositysensor module 610). In some embodiments, the viscosity sensor module 610measures a viscosity of the reference liquid under one or more measuringconditions for calibration.

In some embodiments, the electronic controller 660 is configured tocontrol operations of the cleaning solution source 697. In someembodiments, the electronic controller 660 is configured to controloperations of the gas source 698. In some embodiments, the electroniccontroller 660 is configured to control operations of the referenceliquid source 699. In some embodiments, the electronic controller 660 isconfigured to initiate providing a cleaning solution in response to acompletion of a viscosity measurement. In some embodiments, theelectronic controller 660 is configured to initiate providing a gas inresponse to completion of providing the cleaning solution. In someembodiments, the electronic controller 660 is configured to initiateproviding a reference liquid between two liquid samples. In someembodiments, the electronic controller 660 is configured to initiateproviding one or more of the cleaning solution and the gas in responseto completion of providing the reference liquid.

The viscometer can be used in various applications. In some embodiments,the viscometer is used for determining a molecular size (or a molecularweight) of macromolecules. Intrinsic viscosity is related with the sizeof molecules. Intrinsic viscosity [η] is calculated by the equation:

$\lbrack\eta\rbrack = {\lim\limits_{c->0}\left( \frac{\eta - \eta_{s}}{c\;\eta_{s}} \right)}$

where η_(s) is a viscosity of solvent, c is a concentration of a solute(e.g., macromolecules), η is a viscosity of a solution that includes thesolvent and the solute. In order to measure an intrinsic viscosity,viscosity values of solutions with different concentrations of thesolute is measured. In some embodiments, by extrapolating the measuredviscosity values toward a zero concentration of the solute, an intrinsicviscosity is determined.

In some embodiments, a set of solutions is prepared by mixing amacromolecular solute with a solvent at different concentrations of themacromolecular solute, and viscosity of each solution is measured. Insome embodiments, the set of solutions is prepared off line (e.g.,outside the viscometer). In some other embodiments, the set of solutionsis prepared on-line. In some embodiments, the set of solutions isprepared using a mixer in the viscometer. For example, a first syringeis loaded with a solution at a high concentration of a solute (alsocalled herein a stock solution) and a second syringe is loaded with asolution with a low concentration of the solute or a solution that doesnot include the solute (e.g., a solvent). By changing flow rates atwhich solutions in the first and second syringes are provided, a mixturewith a different concentration of the solute is obtained. In this way,concentration can be changed continuously or in a discrete manner.

The intrinsic viscosity is related with a molecular weight of themacromolecules in accordance with the Mark-Houwink-Sakurada equation:[η]=KM ^(a)where M is the molecular weight and K and a are parameters that dependsolely on a temperature of the solution. Thus, in some embodiments, amolecular weight of a macromolecule (e.g., a protein) is determined fromthe intrinsic viscosity of the solution and values of K and a for thetemperature of the solution using the Mark-Houwink-Sakurada equation. Insome embodiments, the viscometer stores predetermined values of K and afor a plurality of temperatures.

In some embodiments, the viscometer is used for determining a meltingtemperature of proteins (e.g., macromolecular proteins). A meltingtemperature of a protein is defined to be a threshold temperature atwhich the protein becomes denatured. At the melting temperature, theprotein typically loses its function (which is often described as a lossof its efficacy). The melting temperature of the protein is known to berelated with a stability of the protein in solutions. Therefore, themelting temperature of a protein has a significant importance inbiological and chemical reactions. Circular dichroism and differentialscanning calorimetry have been used to measure a melting temperature ofa protein. However, these traditional methods have limitations. Forexample, in many practical applications, protein concentrations are low,which make accurate measurements by these traditional methodschallenging. In addition, a holdup time or duration during which asolution is subject to a constant temperature is an important parameterin determining a melting temperature of proteins. With traditionalmethods, a temperature of the protein is ramped up or down with aconstant scan rate, the holdup time cannot be varied independently,thereby making accurate determination of the melting temperaturechallenging. Furthermore, correlating a change of viscosity of asolution with a melting temperature of a protein in the solution hasremained challenging. In particular, solutions in the traditionalrheometers remain exposed to air, and an evaporation of a solvent in thesolution and premature denaturation of proteins led to inaccurateviscosity measurements. Other traditional methods, such as traditionalmethods based on circular dichroism are not capable of measuringviscosity of a solution with a high protein concentration.

In summary, traditional viscometers measure apparent viscosity, insteadof intrinsic viscosity, and require a large volume of a liquid. Thelarge liquid volume requirement with traditional viscometers alsoincreases a cleaning time and a wasted volume of cleaning solutions.Unlike traditional viscometers, viscometers described herein areconfigured to measure accurately a melting temperature of proteins. Inat least one aspect, a solution is fully enclosed in viscometersdescribed herein, an evaporation of the solution (or a solvent in thesolution) is none. Thus, a solute concentration is precisely preservedfor a high accuracy of viscosity measurement.

In some embodiments, viscosity of a macromolecule is measured as afunction of temperature. FIG. 7 is a chart that illustrates a method ofdetermining a melting temperature in accordance with some embodiments.FIG. 7 shows viscosity of a phosphate buffered saline (PBS) for aplurality of temperatures (indicated with circular markers). As shown inFIG. 7, viscosity of the phosphate buffered saline decreasesmonotonically with an increasing temperature. FIG. 7 also illustratesthat viscosity of a bovine gamma globulin solution (e.g., 3 mg/ml bovinegamma globulin solution) decreases with an increasing temperature for atemperature range of 62° C. and below (indicated with square markers).FIG. 7 further illustrates that viscosity of the globulin solutionlevels off or increases at 64° C. and above. The temperature at thepoint of leveling off or increase in viscosity is related to the meltingtemperature. Thus, in this example, a melting temperature of a globulinis determined to be 64° C.

FIGS. 8A-8C are flow charts representing a method 800 of measuring aviscosity of a liquid in accordance with some embodiments.

In some embodiments, each of the following operations is performed bythe viscometer, independent of user intervention (e.g., without userintervention).

In some embodiments, the method includes (802) coupling a syringe with aviscosity sensor (e.g., in FIG. 6B, the syringe 620 is coupled with theviscosity sensor 612 in the viscosity sensor module 610). In someembodiments, the syringe is communicably coupled with the viscositysensor so that the syringe is configured to dispense a liquid to theviscosity sensor (e.g., a liquid flow channel in the viscosity sensor).

In some embodiments, the syringe includes the sample loading interface(e.g., in FIG. 6B, the syringe 620 includes the sample loading interface626).

In some embodiments, the method includes (804) moving the syringebetween a first location for aspirating a test liquid into the syringeand a second location for coupling the syringe to the viscosity sensorindependent of user intervention. The second location is distinct fromthe first location. For example, as shown in FIGS. 6B and 6D, thesyringe 620 is moved between the first location (as shown in FIG. 6D)and the second location (as shown in FIG. 6B).

In some embodiments, moving the syringe between the first location andthe second location includes (806) moving the syringe between the firstlocation and the second location using a transporting device. Forexample, as shown in FIG. 6D, the syringe is moved between the firstlocation and the second location using the transporting device (e.g., arobotic arm). FIG. 6B does not illustrate the transporting device 692,but a person having ordinary skill in the art would understand that thetransporting device 692 can move the syringe from the first locationillustrated in FIG. 6D to the second location illustrated in FIG. 6B.

In some embodiments, the method includes (808) aspirating the testliquid into the syringe independent of user intervention. In someembodiments, as shown in FIG. 6D, the dispensing mechanism 630 is usedto aspirate a test liquid into the syringe 620 by pulling a plunger ofthe syringe 620. In some embodiments, the test liquid is stored in apressurized container and is forced into the syringe 620 without usingthe dispensing mechanism 630.

The method includes (810) receiving, at a viscometer comprising aviscosity sensor (e.g., the viscosity sensor 612, FIG. 6B) with a liquidflow channel, a liquid from a syringe into the liquid flow channel at aknown flow rate. The viscometer includes a dispensing mechanism (e.g.,the dispensing mechanism 630, FIG. 6B) and an electronic controller(e.g., the electronic controller 660, FIG. 6B). At least two pressuresensors are positioned along the liquid flow channel and configured tomeasure a pressure drop of the liquid flowing through the liquid flowchannel (e.g., FIG. 2B). The electronic controller (e.g., the electroniccontroller 660, FIG. 6B) is configured to control operations of thedispensing mechanism and receive and process data. The dispensingmechanism is configured to couple with the syringe and cause dispensingof a liquid in the syringe to the viscosity sensor at the known flowrate.

The method includes (812) measuring a viscosity of the liquid. In someembodiments, the viscosity of the liquid is measured using the viscositysensor module 610 (or the viscosity sensor 612 in the viscosity sensormodule 610, FIG. 6B). Measurement of a viscosity of a liquid isdescribed above with respect to FIG. 2B, and is not repeated forbrevity.

In some embodiments, the viscometer includes a sample loading interface(e.g., the sample loading interface 626, FIG. 6B) through which theviscometer is configured to receive the liquid.

In some embodiments, a plurality of liquid flow channels is defined inthe viscosity sensor and at least two pressure sensors are positionedalong each of two or more liquid flow channels of the plurality ofliquid flow channels. For example, liquid flow channels 31 shown in FIG.2C are defined in a single viscosity sensor.

In some embodiments, the viscometer includes a viscosity sensor modulethat includes a plurality of viscosity sensors. For example, in someembodiments, each liquid flow channel 31 illustrated in FIG. 2C is usedby a respective viscosity sensor. In some embodiments, the plurality ofviscosity sensors is located in a single viscosity sensor module. Insome embodiments, the multiple viscosity sensors increase a dynamicrange of shear rates that can be measured by the viscometer. In someembodiments, the dynamic range of shear rates is increased by includingmultiple viscosity sensor modules, multiple syringes, and multipledispensing modules. For example, a first combination of a firstviscosity sensor module and a first syringe is configured to measure afirst range of shear rates, and a second combination of a secondviscosity sensor module and a second syringe is configured to measure asecond range of shear rates that is distinct from the first range ofshear rates. Combining the two ranges of shear rates allows viscositymeasurements in a wider range of shear rates. This is desirable incertain applications. In some embodiments, a combination of multipleviscosity sensor modules, multiple syringes, and multiple dispensingmodules is used to increase a throughput of viscosity measurements.

In some embodiments, the liquid includes (814) a polymer (e.g., amacromolecule), and the method further includes determining a molecularweight of the polymer.

In some embodiments, the liquid includes (816) a protein, and the methodfurther includes determining a melting temperature of the protein.

In some embodiments, the method includes (818) determining viscosityvalues of the liquid at a plurality of temperatures, the liquidincluding proteins of a first type (e.g., globular proteins); anddetermining a melting temperature of the proteins of the first type fromviscosity values of the liquid at the plurality of temperatures. In someembodiments, determining the melting temperature of the proteins of thefirst type includes identifying a temperature at which viscosity of theproteins of the first type increases or levels off with an increasingtemperature. In some embodiments, determining the melting temperature ofthe proteins of the first type includes identifying an inflection pointin a viscosity-temperature plot for the proteins of the first type.

In some embodiments, the method includes (820) determining viscosityvalues of a second liquid at a plurality of temperatures. The secondliquid includes proteins of a second type (e.g., fibrous proteins). Themethod also includes determining a melting temperature of the proteinsof the second type from viscosity values of the second liquid at theplurality of temperatures. Details of determining the meltingtemperature of the proteins of the first type are applicable todetermining the melting temperature of the proteins of the second type,and thus, are not repeated for brevity.

In some embodiments, the method includes (822) controlling a temperatureof the viscosity sensor. In some embodiments, controlling thetemperature includes (824) operating one or more temperature controldevices (e.g., one or more thermoelectric heating or cooling devices).

In some embodiments, the method includes (826) maintaining thetemperature of the viscosity sensor at a first temperature andmaintaining the temperature of the syringe at a second temperaturedistinct from the first temperature. In some embodiments, the methodincludes maintaining the temperature of the viscosity sensor and thetemperature of the syringe at a same temperature.

In some embodiments, the method includes (828) controlling a temperatureof the syringe. In some embodiments, controlling the temperatureincludes operating one or more temperature control devices (e.g., one ormore thermoelectric heating or cooling devices).

In some embodiments, the method includes (830) mixing, at theviscometer, the liquid with a solvent to obtain a mixed solution. Aconcentration of a solute in the mixed solution is distinct from aconcentration of the solute in the liquid. The method also includesmeasuring a viscosity of the mixed solution. The method further includesrepeating the mixing and the measuring to obtain viscosity values of themixed solution for a plurality of concentrations of the solute. In someembodiments, the method includes determining intrinsic viscosity of theliquid from viscosity values of the mixed solutions. In someembodiments, determining intrinsic viscosity of the liquid includesextrapolating viscosity values of the mixed solutions to obtain a likelyviscosity value for a solution that does not include the solute.

In some embodiments, the method includes (832) moving at least a portionof the liquid in the liquid flow channel back to the syringe. Thisenables multiple viscosity measurements with a limited volume of aliquid. For example, in some embodiments, viscosity of the liquid ismeasured at a plurality of temperatures using the liquid moved back fromthe liquid flow channel into the syringe.

In some embodiments, the method includes (834), prior to measuring theviscosity of the liquid, identifying a flow rate that satisfies pressurecriteria for the at least two pressure sensors. For example, in someembodiments, the viscometer determines whether a fully developed flow ofthe liquid is present in a liquid flow channel of a viscosity sensorprior to measuring the viscosity of the liquid.

In some embodiments, the method includes (836) dispensing a continuousstream of liquids to the viscosity sensor. The continuous stream ofliquids includes two or more batches of test liquids. Any two adjacentbatches of test liquids, of the two or more batches of test liquids, areseparated by at least one inert liquid immiscible with the two adjacentbatches of test liquids. The two adjacent batches are adjacent to eachother in a sequence of batches in the continuous stream of liquids.However, in some embodiments, the two adjacent batches do not contacteach other, because the two adjacent batches are separated by animmiscible liquid.

In some embodiments, the method includes (838) dispensing a cleaningsolution through the liquid flow channel of the viscosity sensor. Insome embodiments, dispensing the cleaning solution through the liquidflow channel of the viscosity sensor includes cleaning the liquid flowchannel of the viscosity sensor. In some embodiments, the methodincludes dispensing the cleaning solution to a selection valve. In someembodiments, dispensing the cleaning solution to the selection valveincludes cleaning the selection valve. In some embodiments, the methodincludes dispensing the cleaning solution to the syringe. In someembodiments, dispensing the cleaning solution to the syringe includescleaning the syringe.

In some embodiments, the method includes (840) flowing gas through theliquid flow channel. In some embodiments, flowing gas through the liquidflow channel includes drying the liquid flow channel. In someembodiments, the method includes providing the gas to a selection valve.In some embodiments, providing the gas to the selection valve includesdrying the selection valve. In some embodiments, the method includesproviding the gas to the syringe. In some embodiments, providing the gasto the syringe includes drying the syringe. In some embodiments, the gascomprises clean dry air. In some embodiments, the gas comprises drynitrogen gas.

In some embodiments, the method includes diagnosing the viscometer usinga dry air with a preset pressure, which is used for determining a healthof the viscometer. For example, in some embodiments, a pressureregulated dry air is directed to the viscometer. The viscometer thenmeasures pressures in the chip (e.g., using the at least two pressuresensors). In some embodiments, the measured pressures are converted intoa flow rate using the known viscosity of the air. By comparing themeasured flow rate with a predetermined flow rate of a healthyviscometer chip (or a predetermined range of flow rates of a healthyviscometer chip), the health of the viscometer (and the path connectingthe chip and the air source) is diagnosed prior to injecting samples.Checking the health of the viscometer prior to injecting a sample isuseful. In particular, checking the health of the viscometer prior toinjecting a sample avoids wasting a precious sample due to malfunctionof the viscometer.

In some embodiments, the method includes coupling the viscometer with asource of gas. The gas is regulated dry gas. The method also includesproviding the gas through the liquid flow channel; performing ameasurement with the viscosity sensor; and determining whether theviscosity sensor is operating within predefined criteria based on themeasurement performed with the viscosity sensor (e.g., whether theliquid flow channel is blocked and/or narrowed).

In some embodiments, performing the measurement with the viscositysensor includes measuring pressures of the gas within the viscositysensor. For example, when a flow channel is at least partially blocked,the pressures measured by the viscosity sensor (e.g., two or morepressures sensors of the viscometer) are higher than the pressure of thegas at the source.

In some embodiments, performing the measurement with the viscositysensor includes converting the pressures of the gas to a flow rate ofthe gas. For example, when a flow channel is at least partially blocked,the flow rate is less than a predetermined flow rate (e.g., the flowrate of a healthy viscometer).

In some embodiments, the method includes (842) calibrating theviscometer using a preselected reference liquid independent of a userinput. For example, in some embodiments, a viscosity of a preselectedreference liquid is measured and the measured viscosity is compared witha viscosity, of the preselected referenced liquid, stored prior to themeasurement (also called herein a previously known viscosity of thepreselected reference liquid). In some embodiments, subsequent viscositymeasurements are adjusted based on a difference between the measuredviscosity and the previously known viscosity of the preselectedreference liquid. In some embodiments, the viscosity of the preselectedreference liquid is measured at multiple temperatures, and measuredviscosity values at the multiple temperatures are used to calibrate theviscometer. In some embodiments, multiple preselected reference liquidsare used to calibrate the viscometer.

In some embodiments, the method includes (844) measuring one or more of:a pH, a density, and a conductivity of the liquid. In some embodiments,the pH and the conductivity of the liquid are concurrently measured. Insome embodiments, the pH and the viscosity of the liquid areconcurrently measured. In some embodiments, the conductivity and theviscosity of the liquid are concurrently measured. In some embodiments,the density and the viscosity of the liquid are concurrently measured.In some embodiments, the density and the pH of the liquid areconcurrently measured. In some embodiments, the density and theconductivity of the liquid are concurrently measured.

The foregoing description, for purpose of explanation, has beendescribed with reference to specific embodiments. However, theillustrative discussions above are not intended to be exhaustive or tolimit the invention to the precise forms disclosed. Many modificationsand variations are possible in view of the above teachings. Theembodiments were chosen and described in order to best explain theprinciples of the invention and its practical applications, to therebyenable others skilled in the art to best utilize the invention andvarious embodiments with various modifications as are suited to theparticular use contemplated.

What is claimed is:
 1. A viscometer, comprising: a dispensing mechanismconfigured to cause dispensing of a liquid at a known flow rate from afirst syringe to a viscosity sensor with a liquid flow channel and atleast two pressure sensors positioned along the liquid flow channel andconfigured to measure a pressure drop of the liquid flowing through theliquid flow channel, including a first pressure sensor positioned tomeasure a pressure at a first location of the liquid flow channel and asecond pressure sensor positioned to measure a pressure at a secondlocation of the liquid flow channel, wherein the dispensing mechanism isconfigured to couple with the first syringe, and the first syringe iscoupled with the viscosity sensor; an electronic controller configuredto control operations of the dispensing mechanism and receive andprocess data from the viscosity sensor; and a sample loading interfacethrough which the viscometer is configured to receive the liquid; and anautosampler configured to move an injector syringe between a locationfor aspirating a test liquid into the injector syringe and a locationfor coupling the injector syringe with the sample loading interface toload the test liquid into the first syringe.
 2. The viscometer of claim1, further comprising a selection valve coupled with the viscositysensor and the first syringe and located between the viscosity sensorand the first syringe.
 3. The viscometer of claim 1, wherein a barrel ofthe first syringe includes a side port through which the barrel iscoupled with the sample loading interface.
 4. The viscometer of claim 1,wherein the viscometer is configured to aspirate the test liquid intothe injector syringe independent of user intervention.
 5. The viscometerof claim 1, further comprising a viscosity sensor module that includes aplurality of viscosity sensors.
 6. The viscometer of claim 1, wherein aplurality of liquid flow channels is defined in the viscosity sensor andat least two pressure sensors are positioned along each of two or moreliquid flow channels of the plurality of liquid flow channels.
 7. Theviscometer of claim 1, further comprising a temperature control device,wherein the temperature control device is coupled with the electroniccontroller and the electronic controller is configured to control thetemperature control device; determine viscosity values of the liquid ata plurality of temperatures, the liquid including proteins of a firsttype; and determine a melting temperature of the proteins of the firsttype from viscosity values of the liquid at the plurality oftemperatures.
 8. The viscometer of claim 7, wherein the electroniccontroller is configured to: determine viscosity values of a secondliquid at a plurality of temperatures, the second liquid includingproteins of a second type; and determine a melting temperature of theproteins of the second type from viscosity values of the second liquidat the plurality of temperatures.
 9. The viscometer of claim 1, furthercomprising a mixer coupled with the electronic controller and configuredto mix the liquid with a solvent to obtain a mixed solution, wherein aconcentration of a solute in the mixed solution is distinct from aconcentration of the solute in the liquid, wherein the electroniccontroller is configured to: measure a viscosity of the mixed solution;and initiate repeated mixing and measuring to obtain viscosity values ofthe mixed solution for a plurality of concentrations of the solute. 10.The viscometer of claim 1, including a sample injector, the sampleinjector being configured to dispense a continuous stream of liquids tothe viscosity sensor, the continuous stream of liquids including two ormore batches of test liquids, wherein any two adjacent batches of testliquids, of the two or more batches of test liquids, are separated by atleast one inert liquid immiscible with the two adjacent batches of testliquids.
 11. The viscometer of claim 1, further comprising a pumpconfigured to dispense a cleaning solution through the liquid flowchannel of the viscosity sensor.
 12. The viscometer of claim 1, whereinthe viscometer is configured to couple with a source of gas and providethe gas through the liquid flow channel.
 13. The viscometer of claim 12,wherein the gas is regulated dry gas.
 14. The viscometer of claim 13,wherein the viscometer is configured to determine an operation status ofthe viscosity sensor based on one or more measurements for the regulateddry gas.
 15. The viscometer of claim 1, wherein the viscometer isconfigured to self-calibrate by using a preselected reference liquid.16. The viscometer of claim 1, further comprising one or more of: a pHmeter, a density meter, and a conductivity meter.
 17. A method forperforming a viscosity measurement, the method comprising: moving, usingan autosampler, an injector syringe between a first location foraspirating a liquid into the injector syringe and a second location forcoupling the injector syringe with a sample loading interface to loadthe liquid into a first syringe, wherein the second location is distinctfrom the first location; coupling the injector syringe with a viscositysensor of a viscometer through the first syringe, wherein the viscositysensor is with a liquid flow channel and at least two pressure sensorspositioned along the liquid flow channel and configured to measure apressure drop of the liquid flowing through the liquid flow channel,including a first pressure sensor positioned to measure a pressure at afirst location of the liquid flow channel and a second pressure sensorpositioned to measure a pressure at a second location of the liquid flowchannel; receiving the liquid from the injector syringe into the firstsyringe through the sample loading interface; dispensing, with adispensing mechanism coupled with the first syringe and an electroniccontroller, the liquid into the liquid flow channel of the viscositysensor at a known rate; and measuring a viscosity of the liquid.
 18. Themethod of claim 17, further comprising: coupling the viscometer with asource of gas, wherein the gas is regulated dry gas; providing the gasthrough the liquid flow channel; performing a measurement with theviscosity sensor; and determining whether the viscosity sensor isoperating within predefined criteria based on the measurement performedwith the viscosity sensor.
 19. The method of claim 18, whereinperforming the measurement with the viscosity sensor includes measuringpressures of the gas within the viscosity sensor.
 20. The method ofclaim 19, wherein performing the measurement with the viscosity sensorincludes converting the pressures of the gas to a flow rate of the gas.